The overall objectives of the grant application are as follows: 1. To develop and validate new methods for a) characterizing the enterohepatic circulation of bile acids and related compounds in health and disease, and b) characterizing hepatobiliary and intestinal function in health and disease. 2. To develop a comprehensive steady-state and dynamic model for the enterohepatic circulation of all major bile acids in health in man which will encompass synthesis, conjugation, deconjugation, and reconjugation; dehydroxylation, dehydrogenation, and subsequent hepatic reduction; sulfation, desulfation, and resulfation. 3. To define the structure-activity relationships for bile acid transport by liver. 4. To define the physical, chemical, and physiological properties of nor bile acids. 5. To define the determinants of biliary lipid secretion in man, especially as they relate to the formation of supersaturated gallbladder bile and the use of chenodeoxycholic acid for gallstone dissolution. 6. To begin to develop a comprehensive steady-state model for the enterohepatic circulation of all bile acids in certain liver diseases. 7. To develop new therapeutic approaches to intestinal diseases associated with perturbed bile acid metabolism, e.g. bile acid diarrhea and fatty acid diarrhea. 8. To begin exploratory studies on the relationship, if any, between enteric bacterial biotransformation of bile acids and colon cancer. 9. To characterize the biliary secretion of copper in health and disease.